National Toxicology Program

Selected toxicity information from HSDB, one of the National Library of Medicine's databases. ¹

Names (NTP)

• Semicarbazide hydrochloride
• HYDRAZINECARBOXAMIDE MONOHYDROCHLORIDE (9CI)

Human Toxicity Excerpts

• None found

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Non-Human Toxicity Excerpts

• LABORATORY ANIMALS: Acute Exposure: Administration of 200 mg/kg to acute spinal cats resulted in gradual and complete depression of dorsal root reflex and potential..., also decreased long-latency. Time course of these effects correlated with time course of induced depletion of gamma-aminobutyric acid in spinal cord. [Bell JA, Anderson EG; Brain Res 43 (1): 161 (1972) ]**PEER REVIEWED**
  
• LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: Fourteen chemicals of varied uses were tested for carcinogenicity by oral administration in male and female Charles River CD rats. ...Semicarbazide hydrochloride /was/ not carcinogenic under the test conditions. [Weisburger EK et al; J Natl Cancer Inst 67 (1): 75-88 (1981) ]**PEER REVIEWED**
  
• LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: ... Admin to 25 male and 25 female 6-wk old Swiss mice for lifetime as 0.0625% solution in drinking water. Average daily intakes...3.3 mg/female and 4.8 mg/male. ... Tumors of vascular origin ... in 9/50 ... females, compared with 5/99 ... controls, and in 3/50 ... males, compared with 6/99 ... controls. ... Including 6 angiosarcomas and 2 angiomas of liver. ... In females, 37 lung tumors occurred in 25/50 ... compared with 31 in 21/99 female controls...no increase in incidence of lung tumors in treated males. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V12 211 (1976)]**PEER REVIEWED**
  
• LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: ...6-8-wk old female DD mice were fed diet containing 0.1%...for 7 mo. at end of treatment, 8 survivors were killed and examined for lung tumors: 6 mice had total of 8 lung tumors, compared with 1 tumor in 20 controls. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V12 211 (1976)]**PEER REVIEWED**
  
• LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: Administration of 0.0625% carbamylhydrazine hydrochloride in the drinking water of 6 wk old, randomly bred Swiss albino mice for the remainder of their lifetimes, enhanced the development of tumors of the lungs and blood vessels. As compared with untreated controls, the incidence of lung tumors rose from 21-50% in the females and from 23-30% in the males, while the incidence of blood vessel tumors increased from 5-18% in females, but not in males. The study proves... the tumorigencity of this important industrial-laboratory chemical. [Toth B et al; Eur J Cancer 11 (1): 17-22 (1975) ]**PEER REVIEWED**
  
• LABORATORY ANIMALS: Developmental or Reproductive Toxicity: Administration of 50 or 100 mg/day to pregnant Sprague-Dawley rats on days 10-16 of gestation produced high incidence of resorption in dams and of cleft palates in pups. Susceptibility of dams to cleft palate in offspring was greatest on days 12-15 of gestation. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V12 212 (1976)]**PEER REVIEWED**
  
• LABORATORY ANIMALS: Developmental or Reproductive Toxicity: /Investigators/... injected 2.0 mg ... on 6th day into yolk and observed bent tarsometatarsal and tibiotarsal bones and malformed beaks in 14-day-chick embryos. [Shepard, T. H. Catalog of Teratogenic Agents. 3rd ed. Baltimore, MD.: Johns Hopkins University Press, 1980., p. 298]**PEER REVIEWED**
  
• LABORATORY ANIMALS: Developmental or Reproductive Toxicity: A total of 295 pregnant rats were used in 2 different experimental procedures. Five groups of rats were injected intraperitoneally (ip) with 0, 50, 75, 100, or 150 mg/kg of semicarbazide hydrochloride (SC) dissolved in 1 mL saline, on days 5, 7, 10, 13, or 15 of gestation. In the other experimental group, pregnant rats were injected ip with 0 or 17 mg/kg/day SC throughout gestation. All experimental and control animals were either sacrificed on day 21 of gestation (190 animals) or allowed to deliver (105 animals) and their fetuses and offspring were observed for malformations and mortality rate. SC was most embryotoxic on day 7 and 10 of gestation at all doses. Fetal weight was significantly decreased at all doses given on days 5, 7, or 10 of gestation, and this effect was observed on all days of gestation with the 75, 100, and 150 mg/kg doses. There was an increase of maternal deaths with the 150 mg/kg SC dose. Most abnormalities in the 21-day-old fetuses were found in the brain, kidney, intestines, or liver. Incomplete ossification was observed in the skull and sternum of fetuses and also rib anomalies were found. A high percentage of hydronephrosis appeared in the fetuses whose mothers were treated during development period. A statistically significant decrease in the number of implantations and live fetuses resulted from treatment with 17 mg/kg/day SC throughout gestation. The malformations found in the fetuses whose mothers were injected with 17 mg/kg/day SC during gestation were similar to the ones found on the specific-day treatment although liver hemorrhages and hydronephrosis were less frequent. It is concluded that SC was toxic and/or teratogenic in rats at all doses administered. [de la Fuente M; Biol Neonate 49:150-157 (1986) ]**PEER REVIEWED**
  
• LABORATORY ANIMALS: Neurotoxicity: An antivitamin B6, such as semicarbazide (SC), produces running fits as well as tonic and clonic convulsions in mammals. [Yamashita J, Hirata Y; J Nutr Sci Vitaminol 23 (5): 467-70 (1977) ]**PEER REVIEWED**
  
• GENOTOXICITY: In the new in vitro mutagenicity tests commissioned by /the European Food Safety Authority/, semicarbazide showed weak mutagenic activity mainly in the absence of a metabolic activating system. Positive results were obtained in Salmonella typhimurium strains detecting base pair substitutions (TA1535 and TA100) and in the mouse lymphoma tk forward mutation system. The other new study showed weak mutagenic activity only in Salmonella typhimurium strain TA 1535 in the absence but not in the presence of a metabolic activating system. The available results from an ongoing clastogenicity study in cultured mammalian cells are inconclusive and a second trial is being conducted. In vivo, in an earlier study on a series of hydrazine derivative, the ip administration of semicarbazide did not induce DNA damage, as measured by alkaline elution, in liver and lung tissue of mice, whereas positive results were obtained with chemically related genotoxic compounds. ...It is apparent that semicarbazide is weakly genotoxic in some test systems in vitro. The limited in vivo experimental data available are insufficient to assess whether the activity observed in vitro is also expressed in vivo. /Semicarbazide/ [European Food Safety Authority; Statement of the Scientific Panel on Food Additives, Flavorings, Processing Aids and Materials in Contact with Food updating the advice available on semicarbazide in packaged foods p.6 (October 2003). ]**PEER REVIEWED**
  
• GENOTOXICITY: Semicarbazide hydrochloride (0.1 M in glass-distilled water), on injection, showed mutagenic action on the spermatocyte chromosomes of the grasshopper, Spathosternum prasiniferum. Aberrations such as chromatid and chromosome breaks, translocations, fragments and bridges were encountered. The sex chromosome and the long autosomes were affected. Semicarbazide, perhaps, reacts with DNA and the chromosome in a way similar to that of hydroxylamine and hydrazines. [Bhattacharya K; Mutat Res 40 (3): 237-42 (1976) ]**PEER REVIEWED**
  
• OTHER TOXICITY INFORMATION: /According to the European Food Safety Authority Scientific Panel/ semicarbazide appears to be only a weak carcinogen. It did not cause cancer in rats. In mice, increases in tumors that are commonly observed in untreated mice (tumors of the lung and blood vessels) were seen in treated females but not in treated males. The dose at which these tumors were observed was approximately 100 mg/kg bw/day given over a lifetime. It is also noted that semicarbazide is one of the weakest carcinogens among several hydrazines that have been tested in mice. /Semicarbazide/ [European Food Safety Authority; Statement of the Scientific Panel on Food Additives, Flavorings, Processing Aids and Materials in Contact with Food updating the advice available on semicarbazide in packaged foods p.6 (October 2003). ]**PEER REVIEWED**
  

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Human Toxicity Values

• None found

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Non-Human Toxicity Values

• LD50 Mouse oral 225 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2918]**PEER REVIEWED**
  
• LD50 Mouse ip 145 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2918]**PEER REVIEWED**
  
• LD50 Mouse sc 167 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2918]**PEER REVIEWED**
  

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Absorption, Distribution and Excretion

• ... Binds to cytosine residues in RNA, to deoxycytosine residues in DNA in vitro and to cytosine and deoxycytosine nucleosides [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V12 212]**PEER REVIEWED**
  

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Metabolism/Metabolites

• None found

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TSCA Test Submissions

• None found

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Footnotes

¹ Source: the National Library of Medicine's Hazardous Substance Database, 10/28/2007.